Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data.

OBJECTIVE: Genotype imputation is a commonly used technique that infers un-typed variants into a study's genotype data, allowing better identification of causal variants in disease studies. However, due to overrepresentation of Caucasian studies, there's a lack of understanding of genetic basis of health-outcomes in other ethnic populations. Therefore, facilitating imputation of missing key-predictor-variants that can potentially improve a risk health-outcome prediction model, specifically for Asian ancestry, is of utmost relevance. METHODS: We aimed to construct an imputation and analysis web-platform, that primarily facilitates, but is not limited to genotype imputation on East-Asians. The goal is to provide a collaborative imputation platform for researchers in the public domain towards rapidly and efficiently conducting accurate genotype imputation. RESULTS: We present an online genotype imputation platform, Multi-ethnic Imputation System (MI-System) (https://misystem.cgm.ntu.edu.tw/), that offers users 3 established pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1 for conducting imputation analyses. In addition to 1000 Genomes and Hapmap3, a new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. MI-System further offers functions to create customized reference panels to be used for imputation, conduct quality control, split whole genome data into chromosomes, and convert genome builds. CONCLUSION: Users can upload their genotype data and perform imputation with minimum effort and resources. The utility functions further can be utilized to preprocess user uploaded data with easy clicks. MI-System potentially contributes to Asian-population genetics research, while eliminating the requirement for high performing computational resources and bioinformatics expertise. It will enable an increased pace of research and provide a knowledge-base for genetic carriers of complex diseases, therefore greatly enhancing patient-driven research. STATEMENT OF SIGNIFICANCE: Multi-ethnic Imputation System (MI-System), primarily facilitates, but is not limited to, imputation on East-Asians, through 3 established prephasing-imputation pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1, where users can upload their genotype data and perform imputation and other utility functions with minimum effort and resources. A new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. Utility functions include (a) create customized reference panels, (b) conduct quality control, (c) split whole genome data into chromosomes, and (d) convert genome builds. Users can also combine 2 reference panels using the system and use combined panels as reference to conduct imputation using MI-System.

Epiretinal Membrane Detection at the Ophthalmologist Level using Deep Learning of Optical Coherence Tomography.

PURPOSE: Previous deep learning studies on optical coherence tomography (OCT) mainly focused on diabetic retinopathy and age-related macular degeneration. We proposed a deep learning model that can identify epiretinal membrane (ERM) in OCT with ophthalmologist-level performance. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 3,618 central fovea cross section OCT images from 1,475 eyes of 964 patients. METHODS: We retrospectively collected 7,652 OCT images from 1,197 patients. From these images, 2,171 were normal and 1,447 were ERM OCT. A total of 3,141 OCT images was used as training dataset and 477 images as testing dataset. DL algorithm was used to train the interpretation model. Diagnostic results by four board-certified non-retinal specialized ophthalmologists on the testing dataset were compared with those generated by the DL model. MAIN OUTCOME MEASURES: We calculated for the derived DL model the following characteristics: sensitivity, specificity, F1 score and area under curve (AUC) of the receiver operating characteristic (ROC) curve. These were calculated according to the gold standard results which were parallel diagnoses of the retinal specialist. Performance of the DL model was finally compared with that of non-retinal specialized ophthalmologists. RESULTS: Regarding the diagnosis of ERM in OCT images, the trained DL model had the following characteristics in performance: sensitivity: 98.7%, specificity: 98.0%, and F1 score: 0.945. The accuracy on the training dataset was 99.7% (95% CI: 99.4 - 99.9%), and for the testing dataset, diagnostic accuracy was 98.1% (95% CI: 96.5 - 99.1%). AUC of the ROC curve was 0.999. The DL model slightly outperformed the average non-retinal specialized ophthalmologists. CONCLUSIONS: An ophthalmologist-level DL model was built here to accurately identify ERM in OCT images. The performance of the model was slightly better than the average non-retinal specialized ophthalmologists. The derived model may play a role to assist clinicians to promote the efficiency and safety of healthcare in the future.

The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study.

BACKGROUND: Several previous studies reported a greater prevalence of dry eye syndrome (DES) among patients with psychiatric diseases. The aim of this study is to investigate the prevalence and risk factors of DES in patients with psychiatric disorders (PD) using nationwide population-based data in Taiwan. METHODS: This population-based cohort study retrospectively identified patients with PD from 1997 to 2011. Patients with both PD and DES served as the DES cohort, and PD patients without DES comprised the non-DES cohort. PD was defined as a diagnosis of PD (ICD-9-CM 290-319) made by psychiatrists only, with at least three consecutive outpatient visits or at least one inpatient visit. DES was defined as a diagnosis of DES (ICD-9-CM 375.15) and a prescription for an eye lubricant (anatomical therapeutic chemical code, ATC code: S01XA). The main outcome measures were the prevalence of DES in these patients and associated risk factors. RESULTS: A total of 75,650 patients with PD (3665 in the DES cohort and 71,985 in the non-DES cohort) were included in the final analysis. The majority of patients in the DES group were women (72.6%), compared the non-DES group (57.8%). The mean age of patients in the DES cohort was 62.2 ± 14.9, which was significantly older than those in the non-DES group (50.9 ± 17.5). The patients with DES had a significantly greater likelihood of having dementia, bipolar disorder, depression, and neurotic disorders. Conditional regression analyses revealed that patients with dry eye disease were more likely to have schizophrenia (OR = 1.34), bipolar disorder (OR = 1.9), depression (OR = 1.54), and neurotic disorders (OR = 1.62). In addition, patients with DES were more likely to use 1st generation anti-psychotics (OR = 1.28) and had a lower risk of using 2nd generation anti-psychotics (OR = 0.64). CONCLUSION: The study demonstrated that among PD patients, DES is highly prevalence in certain subtypes of PD, such as depression, bipolar disorder, and neurotic disorders, after adjusting for the comorbidities.

Association between Metformin and a Lower Risk of Age-Related Macular Degeneration in Patients with Type 2 Diabetes.

PURPOSE: This population-based, retrospective cohort study was to investigate whether metformin is associated with a lower risk of subsequent age-related macular degeneration (AMD) in patients with type 2 diabetes. METHODS: Using the Taiwan National Health Insurance Research Database from 2001 to 2013, 68205 subjects with type 2 diabetes were enrolled in the study cohort. Among them, 45524 were metformin users and 22681 were nonusers. The metformin and nonmetformin groups were followed until the end of 2013. Cox regression analyses were used to estimate hazard ratios (HRs) for AMD development associated with metformin use. Confounders included for adjustment were age, sex, and comorbidities (hypertension, hyperlipidemia, coronary artery disease, obesity, diabetic retinopathy, chronic kidney disease, and insulin treatment). Furthermore, propensity score (PS) matching method was used to choose the matched sample, and PS-adjusted Cox regression was performed. Finally, how HRs changed according to metformin treatment duration and dose was also evaluated in the metformin group. RESULTS: After adjusting for confounders, the metformin group had a significantly lower risk of AMD (adjusted HR = 0.54; 95% confidence interval [CI], 0.50-0.58). In the PS-matched sample, the significance remained (adjusted HR = 0.57; 95% CI, 0.52-0.63). In the metformin group, the adjusted HRs for the second (1.5-4 years) and third (≥4 years) tertiles of metformin treatment duration were 0.52 and 0.14, respectively, compared with the first tertile (<1.5 years). We also found significant trends of lower HRs (all p-value for trend <0.05) with increasing total and average doses. CONCLUSIONS: Among patients with type 2 diabetes, those who use metformin are at a significantly lower risk of developing AMD relative to individuals who do not use metformin. Also, the trend of a significantly lower AMD risk was found with a higher dose of metformin.

Clinical Characteristics, Intraoperative Findings, and Surgical Outcomes of Canalicular Laceration Repair with Monocanalicular Stent in Asia.

PURPOSE: To report the epidemiological and clinical data as well as surgical outcomes of canalicular lacerations with Mini-Monoka insertion at a tertiary center in Taiwan and to discuss differences in traumatic pattern, pathogenesis, and surgical outcomes between Taiwan and other countries. METHODS: From 2009 to 2018, all 48 patients who underwent canalicular laceration repair with Mini-Monoka stent at a tertiary center in Taiwan were retrospectively analyzed. Demographic and clinical data and surgical outcomes were recorded. RESULTS: The mean age of the 48 patients was 38 years. Single lower canaliculus was involved in 37 (77.1%) patients, upper canaliculus in 10 (20.8%) patients, and both in 1 (2.1%) patient. The most common etiology was motorcycle accident (41.7%), and all traffic accident injuries accounted for 68.75% of cases. Subgroup classification revealed 64.6% of patients (n=31) were categorized in the deep laceration group, and lower anatomical and functional outcomes were noted in deep laceration. The mean follow-up time was 14.5 months. Overall, the anatomical success rate was 87.5%, and the functional success rate was 91.7% after stent removal. CONCLUSION: Canalicular laceration caused by traffic accidents occurred with a relatively high frequency in Taiwan. Affected patients tended to be middle-aged, and deep laceration accounted for 64.6% of patients. These were contributed by the avulsive eyelid injury mechanism caused by traffic accidents. Furthermore, the deeper lacerated site was located, and the lower anatomical and functional success rates were observed. Early repair after trauma with Mini-Monoka stents achieved good eyelid position (100%) as well as good anatomical (87.5%) and functional (91.7%) success without serious complication.

Association between normal tension glaucoma and the risk of Alzheimer's disease: a nationwide population-based cohort study in Taiwan.

OBJECTIVES: To investigate a possible association between normal tension glaucoma (NTG) and an increased risk of developing Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: NTG group and the comparison group were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013. PARTICIPANTS: A total of 15 317 subjects with NTG were enrolled in the NTG group, and 61 268 age-matched and gender-matched subjects without glaucoma were enrolled in the comparison group. PRIMARY AND SECONDARY OUTCOME MEASURES: Kaplan-Meier curves were generated to compare the cumulative hazard of AD between the two groups. A multivariable Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AD, adjusted for diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke. Furthermore, risk factors for developing AD among the NTG group were investigated. RESULTS: The mean age of the cohort was 62.1±12.5 years. Patients with NTG had significantly higher proportions of diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke than the comparisons. Patients with NTG had a significantly higher cumulative hazard for AD than the comparisons (p<0.0001). In the multivariable Cox regression after adjustment for confounders, the NTG group had a significantly higher risk of AD (adjusted HR 1.52; 95% CI 1.41 to 1.63). Moreover, in the NTG group, when we compared the effects of different types of glaucoma eye drops, none of the eye drops used were significant risk factors or protective factors for AD. CONCLUSIONS: People with NTG are at a significantly greater risk of developing AD compared with individuals without glaucoma. Among patients with NTG, none of the glaucoma eye drops used significantly changed the risk of subsequent AD.

Risk of Ischemic Stroke, Hemorrhagic Stroke, and All-Cause Mortality in Retinal Vein Occlusion: A Nationwide Population-Based Cohort Study.

PURPOSE: To investigate whether the risk of subsequent stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality is increased among retinal vein occlusion (RVO) patients compared to non-RVO patients. METHODS: From the entire population of the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2013, a total of 22919 subjects with RVO were enrolled in the RVO group, and 114595 propensity score (PS)-matched non-RVOs were enrolled in the comparison group. PS matching was based on age, gender, obesity, diabetes, hypertension, hyperlipidemia, coronary artery disease, atrial fibrillation, hyperviscosity syndrome, Charlson comorbidity index, glaucoma, and the use of antithrombotic drugs. A multivariate Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) with a 95% confidence interval (CI) for each of the clinical outcomes, including stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality. Furthermore, we divided the RVO group into the branch retinal vein occlusion (BRVO) group and the central retinal vein occlusion (CRVO) group and separately compared their subsequent risks of the clinical outcomes with those of the comparison group. RESULTS: After adjusting for PS, the RVO group had a significantly higher risk of stroke (adjusted HR = 1.36; 95% CI: 1.32-1.40), ischemic stroke (adjusted HR = 1.36; 95% CI: 1.32-1.40), and hemorrhagic stroke (adjusted HR = 1.34; 95% CI: 1.24-1.44). However, the all-cause mortality did not exhibit significant differences. Furthermore, both the BRVOs and CRVOs had a significantly higher risk of subsequent stroke, ischemic stroke, and hemorrhagic stroke than did the comparisons, whereas all-cause mortality was similar among the groups. CONCLUSIONS: People with RVO are at a significantly greater risk of developing stroke, ischemic stroke, and hemorrhagic stroke. However, RVO does not significantly increase the risk of all-cause mortality.

The association between glaucoma and risk of depression: a nationwide population-based cohort study.

BACKGROUND: Previous cross-sectional studies revealed a higher prevalence of depression among glaucoma patients. However, cohort studies were in lack to build the risk of incident depression after the diagnosis of glaucoma. The aim of our study was to investigate the association between glaucoma and the subsequent risk of developing depression and to assess risk factors associated with depression in glaucoma patients. METHODS: A population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from January 1, 2001 through December 31, 2011. Glaucoma patients (n = 8777) and age- and gender-matched control subjects without glaucoma (n = 35,108) were enrolled in the study. Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent depression between the glaucoma and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the glaucoma patients. RESULTS: Glaucoma patients had a significantly higher cumulative hazard of depression compared to the control group (p-value < 0.0001). The Cox regression model indicated that the glaucoma group had a significantly higher risk of depression (adjusted HR = 1.71). Within the glaucoma group, significant risk factors for depression included age, female, low income, substance abuse, and living alone. However, the use of ß-blocker eye drops and the number of glaucoma medications were not significant risk factors for depression. CONCLUSION: Patients with glaucoma are at significantly greater risk of developing depression. Among glaucoma patients, age, female, low income, substance abuse, and living alone were significant risk factors for depression.

Risk of developing open-angle glaucoma in patients with carotid artery stenosis: A nationwide cohort study.

Whether carotid artery stenosis (CAS) is an independent risk factor for open-angle glaucoma remains unclear. In this study, we investigated the association between CAS and the development of open-angle glaucoma in the Taiwanese population-based cohort derived from a longitudinal database containing claims data from the Taiwan National Health Insurance (NHI) program; this study enrolled 2093 patients with CAS and 8372 patients without CAS matched by age and sex from 1999 to 2010. Diagnoses of open-angle glaucoma (OAG) were identified during a follow-up period lasting through December 31, 2013. A Cox proportional hazards model was applied to evaluate the hazard ratio (HR) for OAG in the CAS cohort compared with the matched cohort. We found that the HR for open-angle glaucoma in the CAS cohort compared with the matched cohort. The adjusted HR for OAG in the CAS cohort was 1.50 (95% confidence interval, 1.11-2.02, P = .008). The Kaplan-Meier analysis revealed that the CAS cohort had a higher cumulative incidence of OAG than did the matched cohort during the follow-up period (log-rank test, P < .001). We concluded that CAS is a significantly independent risk factor for the development of OAG. Our finding is clinically important for the aging population, which has an increasing prevalence of CAS.

Analysis of the Interleukin-6 (-174) Locus Polymorphism and Serum IL-6 Levels with the Severity of Normal Tension Glaucoma.

PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. METHODS: A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. RESULTS: The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06). CONCLUSION: The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.

Paper-based ELISA to rapidly detect Escherichia coli.

Escherichia coli is a generic indicator of fecal contamination, and certain serotypes cause food- and water-borne illness such as O157:H7. In the clinic, detection of bacteriuria, which is often due to E. coli, is critical before certain surgical procedures or in cases of nosocomial infection to prevent further adverse events such as postoperative infection or sepsis. In low- and middle-income countries, where insufficient equipment and facilities preclude modern methods of detection, a simple, low-cost diagnostic device to detect E. coli in water and in the clinic will have significant impact. We have developed a simple paper-based colorimetric platform to detect E. coli contamination in 5h. On this platform, the mean color intensity for samples with 10(5)cells/mL is 0.118±0.002 (n=4), and 0.0145±0.003 (P<0.01⁎⁎) for uncontaminated samples. This technique is less time-consuming, easier to perform, and less expensive than conventional methods. Thus, paper-based ELISA is an innovative point-of-care diagnostic tool to rapidly detect E. coli, and possibly other pathogens when customized as appropriate, especially in areas that lack advanced clinical equipment.

Pharmacokinetics and safety of intravitreal caspofungin.

Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 µg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 µg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 µg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

Aniseikonia following pneumatic retinopexy for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the characteristics of aniseikonia in patients with rhegmatogenous retinal detachment (RD) after pneumatic retinopexy. DESIGN: Prospective, interventional case series study. METHODS: Thirty patients who had undergone pneumatic retinopexy as the initial procedure for rhegmatogenous retinal detachment were selected for this study. The principal outcomes included visual acuity, postoperative aniseikonia measured by the New Aniseikonia Test, anatomical success, and measurement of central retinal thickness using optical coherence topography (OCT). These outcomes were measured postoperatively at 3, 6, and 12 months. RESULTS: The median patient age was 37 years (range, 13-57 years), with 17 cases of macula-off RD and 13 cases of macula-on RD. All of these patients achieved anatomical success, proven by OCT after surgical repair. Three months after pneumatic retinopexy, 18 patients (60.0%) developed micropsic aniseikonia and aniseikonia was diagnosed in 15 patients (88.2%) in the macula-off RD group, leaving 2 patients (11.8%) unaffected. In the macula-on RD group, 3 patients (23.1%) were found to have aniseikonia, while 10 patients (76.9%) were unaffected. The presence of aniseikonia was strongly linked to the difference in central retinal thickness, between the operated eye and the fellow eye, measured at 12 months postoperatively. CONCLUSION: Aniseikonia after pneumatic retinopexy for rhegmatogenous RD may be related to the preoperative macular status. Macula-off RD patients had a higher incidence of aniseikonia, compared to macula-on RD patients, following retina reattachment. There was a moderate to high correlation between the grading of aniseikonia and the difference in central retinal thickness.

Pterygium is related to a decrease in corneal endothelial cell density.

PURPOSE: The aim of this study was to investigate the relationship between pterygium and a decrease in the corneal endothelial cell density (ECD) in patients with unilateral primary pterygium. METHODS: In this retrospective cross-sectional study, 90 consecutive patients with unilateral primary pterygium were enrolled from January 2010 to June 2012. Corneal ECD was measured in both eyes, and the fellow eyes were considered as controls. The relationship between the percentage of pterygium to cornea and a decrease in the ECD was analyzed. An increase in astigmatism in eyes with pterygium was evaluated for association with decreased ECD using the Pearson correlation test. RESULTS: The percentage of pterygium to cornea ranged from 3.5% to 65.2%, with a median of 12.35%. The difference in the corneal ECD between eyes with pterygium and control eyes ranged from +9.6% to -37.7%, with a median of -9.75%. The results of the Pearson correlation statistical test showed a strong logarithmic correlation between a decrease in the corneal ECD and the percentage of pterygium to cornea (R = 0.688, P < 0.001). An increase in astigmatism was correlated with a decrease in the ECD in eyes with pterygium. CONCLUSIONS: Pterygium is related to a decrease in corneal ECD. Surgical intervention should be considered in patients with extensive pterygium involvement in the cornea or a significant increase in astigmatism.

Monitoring the VEGF level in aqueous humor of patients with ophthalmologically relevant diseases via ultrahigh sensitive paper-based ELISA.

The vascular endothelial growth factor (VEGF) level in aqueous humor has been used as an indicator to monitor specific diseases in the retinal ischemic condition. For clinical diagnosis, only about 200 µL of aqueous humor can be collected from the anterior chamber before the threat of anterior chamber collapse. It is necessary to develop an inexpensive diagnostic approach with the characteristics of highly sensitive, short operation duration, and requires small clinical sample quantities. To achieve the main objective of this study, we first prepared bevacizumab to be conjugated with HRP. We then deposited 2 µL aqueous humor from patients with different diseases onto each test zone of paper-based 96-well plates. After the colorimetric results were performed via ELISA protocol, the output signals were recorded using a commercial desktop scanner for analysis. In this study, only 2 µL from the aqueous humor of each patient was required for paper-based ELISA. The mean aqueous VEGF level was 14.4 pg/mL from thirteen patients (N = 13) with senile cataract as the control. However, the mean aqueous VEGF level from other patients with proliferative diabetic retinopathy (N = 14), age-related macular degeneration (N = 17), and retinal vein occlusion (N = 10) showed VEGF increases to 740.1 pg/mL, 383 pg/mL, and 219.4 pg/mL, respectively.

Polymorphism in the TNF-α(-863) locus associated with reduced risk of primary open angle glaucoma.

PURPOSE: Tumor necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiologic and pathogenic effects that lead to tissue destruction. Recent laboratory evidence indicates that TNF-α have either protective or adverse effects on primary open angle glaucoma (POAG). Inheritance of the TNF-α (-863) C allele has been associated with an elevated risk of Alzheimer disease. The neuronal injuries associated with Alzheimer disease have several similarities with the optic nerve changes often seen with POAG. In this study we investigated the possible association between the TNF-α (-863) polymorphism and the development of POAG. METHODS: A total of 234 patients with POAG were recruited and compared with 230 healthy controls in a Chinese population. Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by polymerase chain reaction (PCR) amplification. Patients and controls were genotyped for the A/C polymorphism at position -863 of the TNF-α gene promoter region. RESULTS: The frequency of the TNF-α (-863)A allele (22% versus 30%, respectively; p=0.007) and the carriers of the TNF-α (-863)A allele (37% versus 48%; p=0.017, OR 0.63, 95% CI 0.44-0.92) were lower in POAG patients compared with those in controls. There is a reduced risk of POAG associated with homozygosity for the TNF-α (-863)A allele (AA genotype) compared with that in the control population (AA genotype; 7% versus 11%, respectively, p=0.037; OR 0.5, 95% CI 0.26-0.98). CONCLUSIONS: The TNF-α (-863)A allele polymorphism may be a protective factor in the development of POAG.

Comparison of voriconazole concentration in the aqueous humor and vitreous between non-scraped and scraped corneal epithelium groups after topical 1% voriconazole application.

PURPOSE: To investigate the penetration of topical 1% voriconazole through the cornea into the aqueous humor in New Zealand white rabbits and to determine the effect of mechanical scraping of the corneal epithelium. MATERIALS AND METHODS: The right eyes of 29 New Zealand white rabbits were maintained with the epithelium intact, and the left eyes underwent mechanical epithelium debridement of the central 7.5 mm of the cornea. A loading dose consisted of a drop of 1% voriconazole applied every 5 min for the initial half hour and followed by a maintenance dose consisting of a drop every 20 min, which was applied for about 2 hr. Then, the first sample was obtained 5 min after the first seven doses (loading dose) were given, and then four more samples were taken 5 min after four more subsequent drops (maintenance dose). The samples were analyzed by high performance liquid chromatography. RESULTS: The mean aqueous concentration of voriconazole was 33.44 +/- 5.77 microg/mL 5 min after the loading dose in the non-scraped group and 57.67 +/- 6.77 microg/mL in the scraped group, respectively. The mean aqueous concentration of voriconazole was maintained in a range from 19.97 to 23.70 microg/mL 5 min after the maintenance doses in the non-scraped group and from 44.44 to 49.02 microg/ mL in the scraped group. The mean vitreous concentration of voriconazole ranged from 0.38 to 0.49 microg/mL in the non-scraped group and ranged from 0.72 to 0.94 microg/mL in the scraped group. These levels were statistically significant (P < 0.05) between the scraped and non-scraped groups. CONCLUSIONS: Topically administered voriconazole achieved minimum inhibitory concentrations in the aqueous for all the organisms most commonly involved in fungal endophthalmitis and achieved minimum inhibitory concentrations in the vitreous for some pathogenic fungi. The concentrations of voriconazole were higher in the scraped group than in the non-scraped group.

Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis.

PURPOSE: To report the therapeutic efficacy of intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. DESIGN: Retrospective, single-institution, consecutive case series. METHODS: Microbiologic and medical records were reviewed for patients with positive intraocular culture results or proven pathologic features for fungal organisms and clinically diagnosed fungal endophthalmitis resulting from keratitis. Ten eyes were treated with an intracameral injection of 100 microg voriconazole. Clinical characteristics, treatment, and causative organisms were analyzed. RESULTS: Fusarium and Aspergillus were the most common causative organisms. Voriconazole was injected intracamerally from 1 to 8 times. Of the 7 patients who received 5 or more repeat injections, 6 were caused by Fusarium and 1 by Acremonium. In the remaining 3 patients who were administered 4 or fewer voriconazole injections, the causative organisms were Aspergillus and Alternaria. CONCLUSIONS: Intracameral voriconazole injection may be an effective treatment for fungal endophthalmitis contiguously spreading from keratitis.